ORAL HPV INFECTION IN HIV CO-INFECTED INDIVIDUALS

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。人类免疫缺陷病毒（HIV）已经感染了全世界超过3300万人，导致CD4+T细胞选择性耗竭导致免疫抑制。这种免疫力的缺乏导致许多机会性感染，超过50%的hiv感染者出现涉及口腔的病理。在导致HIV+患者口腔疾病的病原体中，有粘膜萎缩性人乳头瘤病毒（HPV）。虽然HPV不能常规培养，但它是最常见的病毒性性传播疾病。HPV是口腔和生殖器疣、局灶性上皮增生以及很大比例的宫颈、肛门生殖器和口腔鳞状细胞癌的病因。HIV合并感染导致HPV生殖器感染率增加，HPV持久性增加，HPV相关病理（宫颈和肛门发育不良）发生率增加，这更难治疗。同样，初步研究表明，HIV合并感染导致口腔HPV和HPV相关口腔病理（包括口腔癌）的患病率增加。令人惊讶的是，用高活性抗逆转录病毒疗法（HAART）治疗HIV会导致明显的hpv相关口腔疣的增加。这些疣很大，很痛，而且很难治疗。HIV阳性患者继续使用HAART可能导致口腔疣和其他hpv相关口腔病理（如鳞状细胞癌）的发生率大幅增加。迄今为止的研究受到了用于检测HPV感染的分子技术的缺乏或限制范围的限制。因此，对口腔HPV感染的患病率、感染部位和自然史知之甚少。为了预防HPV相关的口腔病理，更好地了解口腔HPV感染，特别是HIV+合并感染的个体，是至关重要的。初步数据表明，利用为检测生殖器HPV而开发的共识PCR引物集检测口腔HPV感染的能力。这些技术可以扩展到检测口腔HPV类型。我们假设可以开发一种基于高通量pcr检测口腔HPV类型的方法，并用于确定HIV+个体队列中口腔HPV感染的患病率和部位。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Human immunodeficiency virus (HIV) has infected over 33 million people worldwide leading to immune suppression from the selective depletion of CD4+T cells. This lack of immunity results in numerous opportunistic infections with over 50% of the HIV-infected individuals developing pathology involving the oral cavity. Among the pathogens responsible for oral disease in HIV+ patients is the mucosatropic human papillomavirus (HPV). Although HPV cannot be routinely cultured, it is the most common viral sexually transmitted disease. HPV is the etiologic agent of oral and genital warts, focal epithelial hyperplasia, and a large proportion of cervical, anogenital, and oral squamous cell carcinomas. HIV co-infection leads to increased rate of HPV genital infection, increased HPV persistence, and increased rates of HPV-related pathology (cervical and anal dysplasia), which is more difficult to treat. Similarly, preliminary studies indicate that HIV co-infection leads to increases in the prevalence of oral HPV and HPV-related oral pathology including oral cancer. Surprisingly, treatment of HIV with highly active anti-retroviral therapy (HAART) has led to increases in apparent HPV-related oral warts. These warts have been large, painful, and difficult to treat. Continued use of HAART for the HIV+ patient may lead to substantial increases in the incidence of oral warts and other HPV-related oral pathology such as squamous cell carcinomas. The studies to date have been limited by the lack of or the restrictive scope of the molecular techniques used to detect HPV infection. Thus, little is known about the prevalence, site of infection and natural history of oral HPV infection. A better understanding of oral HPV infection particularly in the HIV+ co-infected individual is of paramount importance in order to prevent HPV-related oral pathology. Preliminary data demonstrated the ability to detect oral HPV infection utilizing consensus PCR primer sets that were developed for detection of genital HPV. These techniques can be extended to detect oral HPV types. We hypothesize that a high throughput PCR-based method for detecting oral HPV types can be developed and utilized to determine the prevalence and site of oral HPV infection in a cohort of HIV+ individuals.